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EC number: 237-224-5 | CAS number: 13701-64-9
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Toxicity to reproduction
Administrative data
- Endpoint:
- three-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- No data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 966
- Report date:
- 1966
- Reference Type:
- publication
- Title:
- Toxicologic studies on borax and boric acid.
- Author:
- Weir RJ & Fisher RS
- Year:
- 1 972
- Bibliographic source:
- Toxicology and Applied Pharmacology 23: 351 - 364.
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: No guideline specified, but conforms to the standard 3 generation 2 litters per generation multi-generation studies normally used at that time.
- Deviations:
- not applicable
- GLP compliance:
- no
- Remarks:
- Study pre-dates GLP
- Limit test:
- no
Test material
- Reference substance name:
- Boric acid
- EC Number:
- 233-139-2
- EC Name:
- Boric acid
- Cas Number:
- 10043-35-3
- Molecular formula:
- H3BO3
- IUPAC Name:
- Boric acid
- Details on test material:
- - Name of test material: Boric acid
- Physical state: Fine white powder without odour
- Analytical purity: > 99 %
- Stability under test conditions: Stable
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Caesarean-derived from Charles River
Weight at study initiation: (P) Males: 121 - 150 g; Females: 110 - 147 g
- Diet: Ad libitum
- Housing: Prior to initiation of the first breeding phase, the animals were maintained in individual cages and fed their respective diets for 14 weeks until they reached maturity.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Rats were exposed from beginning of the study until sacrifice of parents P0 , and from weaning till sacrifice for the parents of the F1 and F2-generations.
The high dose group P animals were sterile so only controls, low and mid dose groups were taken to the F2 and F3 generations.
DIET PREPARATION
- Mixing appropriate amounts with (Type of food): The test material was incorporated into the basal diet on a weight/weight basis and thoroughly mixed in a twin-shell blender to provide the desired dietary levels. - Details on mating procedure:
- - M/F ratio per cage: 1:2
- Length of cohabitation: 21 days on each occasion
- Any other deviations from standard protocol: This is a three generation multigeneration study with two matings (two litters) per generation. The F1a, F2a and F3a litters were sacrificed at weaning, and the F1b and F2b litters raised and used for breeding, and the F3b killed at weaning.
24 h after birth, the litters were reduced to a maximum of eight pups to be nursed. The F1A litters were discarded when they reached 21 days of age. The parents in the control and two lower test groups were remated to produce their second (F1B) litters. At the time of weaning 16 females and 8 males from the control and two test groups were selected at random and designated as the second parental generation (P2) for continuation of the reproduction study. All excess weanlings were discarded.
The experimental design for the high level test group (0.67 %) was altered due to failure of the P1 parents to produce litters. In order to determine whether the female reproductive system was affected, the P1 females in the high level group were mated with males of the same strain and approximately the same age, which had received only the control diet. The males remained in the breeding cage for 8 h each day. To prevent the males from feeding on teh test diet, no food was available to the animals during the daily mating period. - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- Groups of 8 males and 16 females were used for all generations and were exposed from beginning of the study until sacrifice of parents P0, and from weaning till sacrifice of the F1- and F2-generations.
The high dose group P animals were sterile so only controls, low and mid dose groups were taken to the F2 and F3 generations. - Frequency of treatment:
- Daily
- Details on study schedule:
- This is a three generation multigeneration study with two matings (two litters) per generation. The F1a, F2a and F3a litters were sacrificed at weaning, and the F1b and F2b litters raised and used for breeding, and the F3b killed at weaning.
From beginning of the study until sacrifice of parents P0, and from weaning till sacrifice for the parents of the F1 and F2-generations.
The high dose group P animals were sterile so only controls, low and mid dose groups were taken to the F2 and F3 generations.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 670, 2000 or 6700 ppm boric acid (0, 117, 350 and 1,170 ppm boron) in the diet, equivalent to 0, 34 (5.9), 100 (17.5) and 336 (58.5) mg boric acid (mg B)/kg bw/day.
Basis:
- No. of animals per sex per dose:
- 8 males and 16 females per group
- Control animals:
- yes, plain diet
- Details on study design:
- - Rationale for animal assignment: By stratified randomisation
- Positive control:
- No data
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Weekly
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes, weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data - Oestrous cyclicity (parental animals):
- No data
- Sperm parameters (parental animals):
- Sperm parameters were not done in the high dose group in which histology of the testes were performed.
- Litter observations:
- Number and sex of pups, stillbirths, live births, presence of gross abnormalities, weight gain, physical or behavioural abnormalities; culled to 8 per litter at 42 h after delivery.
Records were maintained on the number of conceptions, number and size of litters, deaths and weights of the pups at 24 h and at weaning. The pups were observed for gross signs of abnormalities. - Postmortem examinations (parental animals):
- After completion of the second cycle (F1B) of the first breeding phase, all P1 animals in the control and two lower test groups were sacrificed (34th week of study). The males in the high level group were sacrificed after completion of the 27th week and the females after completion of the 46th week of the study. Gross necropsies were performed and representative tissues from each rat were preserved in 10 % formalin. Weights were obtained for brain, thyroid, liver, spleen, kidneys, adrenals and testes in all groups; and ovaries and uterus in the high level group. Organ/body weight ratios were obtained. Individual blood samples and pooled samples of brain, liver and kidney (all groups) and testis, ovary and uterus (high level only) were frozen for possible future analysis. The ovaries and uteri preserved from the high level females were examined microscopically.
After completion of the second breeding phase, all P2 animals were sacrificed and after completion of the third breeding phase, all P3 animals were savrificed. Necropsies were performed and the animals were observed for gross signs of pathology. The following tissues from eight males and eight females in the P2 and P3 control and test groups were preserved in 10 % formalin: Brain, thyroid, lung, heart, liver, kidney, adrenal, stomach, pancreas, small intestine, large intestine and gonad. Necropsies were also performed on 5 male and 5 female F3B weanlings from the control and two lower level test groups and representative tissues preserved in 10 % formalin. - Postmortem examinations (offspring):
- No data
- Statistics:
- Terminal body weights, organ weights and organ/body weight ratios for the P1 animals were examined by the analysis of variance, of F-test, at the 5 % probability level. Before completing each F test, the variances were tested for heterogeneity by the method of Bartlett. If the variances were homogeous, the F-test could be applied in the normal fashion, and if a significant F value was obtained those groups significantly different from control could be determined by the method of Scheffe.
In those instances of heterogeneous variances, the samples were examined for extreme values by Sachs' test for rejection of measurements. If no legitimate unbiased adjustment to the variance could be made by rejection of "outliers", comparison test to control was effected by the Fisher-Behrens modified t-test. Breeding indices were analysed by the chi-square test of significance. - Reproductive indices:
- No data
- Offspring viability indices:
- No data
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- effects observed, treatment-related
- Reproductive performance:
- effects observed, treatment-related
Details on results (P0)
Rats of the P0 generation exposed to the high dose of 336 mg/kg bw boric acid (corresponding to a level of 58.5 mg B/kg bw) had reduced bodyweights though food intake was not affected and they were sterile. Microscopic examination of the atrophied testes of all males in this group showed no viable sperm. There were no adverse effects on reproduction reported at exposures of 5.9 and 17.5 mg B/kg bw. The authors reported no adverse effects on fertility, lactation, litter size, progeny weight or appearance in rats exposed to either 5.9 or 17.5 mg B/kg bw. Also, no gross abnormalities were observed in the organs from these dose groups.
Parent females:
The high dose groups of the P0 generation had reduced bodyweight without any effect on food intake. Evidence of decreased ovulation in about half of the ovaries examined from the females exposed to 58.5 mg B/kg bw and only one of 16 females produced a litter when mated with control male animals. There were no adverse effects on reproduction and no gross abnormalities were observed in the organs at exposures of 5.9 and 17.5 mg B/kg bw.
Effect levels (P0)
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 336 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Equivalent to 1170 ppm in the diet. Based on sterility.
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Equivalent to 350 ppm boron in the diet.
- Dose descriptor:
- LOAEL
- Effect level:
- 58.5 mg/kg bw/day
- Based on:
- element
- Sex:
- male/female
- Basis for effect level:
- other: Based on sterility. Testicular atrophy, reduced fertility (no offspring from high dose females mated with untreated males).
- Dose descriptor:
- NOAEL
- Effect level:
- 17.5 mg/kg bw/day
- Based on:
- element
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- body weight and weight gain
- food consumption and compound intake
- other: The authors reported no adverse effects on fertility, lactation, litter size, progeny weight or appearance in rats exposed to either 5.9 or 17.5 mg B/kg bw
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- effects observed, treatment-related
- Mortality / viability:
- not specified
- Body weight and weight changes:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Description (incidence and severity):
- There were no adverse effects on reproduction and no gross abnormalities were observed in the organs at exposures of 5.9 and 17.5 mg B/kg bw.
- Histopathological findings:
- not examined
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not specified
Details on results (F1)
There were no adverse effects on reproduction and no gross abnormalities were observed in the organs at exposures of 5.9 and 17.5 mg B/kg bw.
F1 females:
There were no adverse effects on reproduction and no gross abnormalities were observed in the organs at exposures of 5.9 and 17.5 mg B/kg bw.
F2 males:
There were no adverse effects on reproduction and no gross abnormalities were observed in the organs at exposures of 5.9 and 17.5 mg B/kg bw.
F2 females:
There were no adverse effects on reproduction and no gross abnormalities were observed in the organs at exposures of 5.9 and 17.5 mg B/kg bw.
The high dose group (58.5 mgB/kg bw) males and females showed clinical signs of toxicity with rough fur, scaly tails, respiratory distress and inflamed eyelids.
The high dose group P animals were sterile so only controls, low and mid dose groups were taken to the F2 and F3 generations.
Effect levels (F1)
open allclose all
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Equivalent to 350 ppm boron in the diet.
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 17.5 mg/kg bw/day
- Based on:
- element
- Sex:
- male/female
- Basis for effect level:
- other: There were no adverse effects on reproduction and no gross abnormalities were observed in the organs at exposures of 5.9 and 17.5 mg B/kg bw.
Results: F2 generation
Effect levels (F2)
open allclose all
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Equivalent to 350 ppm boron in the diet.
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- 17.5 mg/kg bw/day
- Based on:
- element
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects in mid and low dose groups in any generation.
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Table for reproductive toxicity:
Parameter |
|
control |
low dose |
medium dose |
High dose |
|
||||||
Generation |
m |
f |
m |
f |
m |
f |
m |
f |
|
|
||
Mortality |
incidence |
P |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
|
F1 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
|
F2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Food consumption |
% of control |
not affected |
|
|
|
|
|
|
|
|
|
|
Body weight gain |
% of control |
|
- |
- |
- |
- |
- |
- |
¯ |
¯ |
|
|
Clinical Observations specify effects |
Incidence |
|
- |
- |
- |
- |
- |
- |
+ |
+ |
|
|
Organ weights |
% of control |
only effect noted was increase in absolute wt. of thyroid in low dose group and relative thyroid wt. in low and mid dose groups (not thought to biologically significant) |
||||||||||
Pathology |
|
|
|
|
|
|
|
|
|
|
|
|
Histopathologic examination specify effects |
Incidence |
Evidence of testis atrophy in high dose males of P0 generation. Evidence in ovary of reduced ovulation in high dose females. |
||||||||||
Reproductive Performance |
|
P0 to F1a |
F1b to F2b |
F2b to F3b |
|
|||||||
cont |
low |
mid |
high |
cont |
low |
mid |
cont |
low |
mid |
|
||
Mating index: (No. pregnant/No. mated) |
% |
62 |
88 |
81 |
0 |
80 |
94 |
94 |
69 |
94 |
94 |
|
Fertility index: No. litters born/No. Pregnant |
% |
100 |
100 |
100 |
- |
100 |
100 |
100 |
91 |
100 |
100 |
|
Number of implantation sites |
Mean |
|
|
|
|
|
|
|
|
|
|
|
Duration of pregnancy |
Mean |
|
|
|
|
|
|
|
|
|
|
|
Birth index |
|
|
|
|
|
|
|
|
|
|
|
|
Live birth index: No.pups alive/No. born |
% |
98 |
96 |
97 |
|
99 |
99 |
98 |
100 |
99 |
99 |
|
Gestation index |
|
|
|
|
|
|
|
|
|
|
|
|
Litter size |
Mean |
12 |
11 |
11 |
|
12 |
13 |
12 |
12 |
13 |
11 |
|
Litter weight |
Mean |
|
|
|
|
|
|
|
|
|
|
|
Pup weight at 24h (g) |
Mean |
7.0 |
7.2 |
6.7 |
|
6.4 |
6.5 |
6.7 |
6.0 |
7.0 |
7.0 |
|
Sex ratio |
Male/female |
6/6 |
6/5 |
5/6 |
|
6/6 |
7/6 |
6/6 |
6/6 |
7/6 |
6/5 |
|
Survival index |
|
|
|
|
|
|
|
|
|
|
|
|
Viability index |
|
|
|
|
|
|
|
|
|
|
|
|
Lactation index: Pup wt. at weaning |
|
55 |
50 |
52 |
|
56 |
53 |
51 |
48 |
51 |
55 |
|
Applicant's summary and conclusion
- Conclusions:
- Rats exposed to the high dose of 336 mg/kg bw boric acid (corresponding to a level of 58.5 mg B/kg bw) were sterile. Microscopic examination of the atrophied testes of all males in this group showed no viable sperm. The authors also reported evidence of decreased ovulation in about half of the ovaries examined from the females exposed to 58.5 mg B/kg bw and only 1/16 matings produced a litter from these high dose females when mated with control male animals. There were no adverse effects on reproduction reported at exposures of 34 and 100 mg/kg bw boric acid (5.9 and 17.5 mg B/kg bw). The authors reported no adverse effects on fertility, lactation, litter size, progeny weight or appearance in rats exposed to either 5.9 or 17.5 mg B/kg bw. Also, no gross abnormalities were observed in the organs examined from either parents or weanlings from these dose groups. Based on these study data, the authors concluded that exposure of rats at levels up to 17.5 mg B/kg bw in the diet in a 3 generation reproduction study was without adverse effect.
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